-
Reumatologia Clinica Apr 2023Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency,...
Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency, which may present with severe haemorrhagic manifestations. LAHPS is usually associated with systemic lupus erythematosus (SLE), or infections and it is more frequent in the paediatric population and female gender. We describe a 42-year-old man with thrombotic antiphospholipid syndrome (APS) on chronic anticoagulation treatment with acenocoumarol who presented with spontaneous intracranial bleeding, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and low factor II levels (after optimal anticoagulation reversal) as a debut of SLE.
Topics: Male; Child; Female; Humans; Adult; Antiphospholipid Syndrome; Lupus Coagulation Inhibitor; Hypoprothrombinemias; Lupus Erythematosus, Systemic; Prothrombin; Hemorrhage
PubMed: 37061283
DOI: 10.1016/j.reumae.2022.02.008 -
Molecules (Basel, Switzerland) Feb 2023The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic...
The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1β, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent.
Topics: Animals; Mice; Acenocoumarol; Anti-Inflammatory Agents; Cyclooxygenase 2; Extracellular Signal-Regulated MAP Kinases; Interleukin-6; Lipopolysaccharides; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Tumor Necrosis Factor-alpha
PubMed: 36903321
DOI: 10.3390/molecules28052075 -
Medical Cannabis and Cannabinoids 2023Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different...
INTRODUCTION
Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles.
METHODS
Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system. The extracts were characterized for their cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition studies with the cannabis extracts and pure cannabinoids (tetrahydrocannabinol [THC] and cannabidiol [CBD]) were performed using pooled, mixed gender human liver microsomes. Tolbutamide and testosterone were used as specific substrates to assess the inhibitory potential of the extracts on CYP2C9 and CYP3A4, and the coumarinic oral anticoagulants warfarin, phenprocoumon, and acenocoumarol were studied as model compounds since in vivo herb-drug interactions have previously been reported for this compound class.
RESULTS
In accordance with the plant chemotypes, two extracts were rich in THC and CBD (at different proportions); one extract contained mostly CBD and the other mostly cannabigerol (CBG). Residual amounts of the corresponding acids were found in all extracts. The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD). The inhibition of CYP3A4 and CYP2C9 by the extract containing mostly CBD was comparable to their inhibition by pure CBD. In contrast, the inhibitory potency of extracts containing both THC and CBD did not correspond to the combined inhibitory potency of pure THC and CBD. Although being structural analogs, the three coumarin derivatives displayed major differences in their herb-drug interaction profiles with the cannabis extracts and the pure cannabinoids.
CONCLUSION
Despite the fact that cannabinoids are the major components in ethanolic, decarboxylated cannabis extracts, it is difficult to foresee their herb-drug interaction profiles. Our in vitro data and the literature-based evidence on in vivo interactions indicate that cannabis extracts should be used cautiously when co-administered with drugs exhibiting a narrow therapeutic window, such as coumarinic anticoagulants, regardless of the cannabis chemotype used for extract preparation.
PubMed: 36814687
DOI: 10.1159/000528465 -
Healthcare (Basel, Switzerland) Dec 2022Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD), and its presence is associated with a higher risk of stroke and...
UNLABELLED
Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD), and its presence is associated with a higher risk of stroke and mortality.
MATERIAL AND METHODS
The FAERC study performed a retrospective multicentre analysis of historical cohorts in which data were collected from arrhythmia diagnosis onwards.
RESULTS
We analysed a Spanish cohort of 4749 patients with CKD (mean eGFR 33.9 mL/min) followed up in the nephrology clinic, observing a 12.2% prevalence of non-valvular AF. In total, 98.6% of these patients were receiving anticoagulant treatment, mainly with coumarins (79.7%). Using direct-acting oral anticoagulants (DOACs) was associated with fewer cerebrovascular events than using acenocoumarol, but in contrast with other studies, we could not corroborate the association of risk of bleeding, coronary events, or death with a type of anticoagulant prescribed.
CONCLUSIONS
Atrial fibrillation is highly prevalent in renal patients. Direct-acting anticoagulants seem to be associated with fewer ischemic-embolic complications, with no differences in bleeding, coronary events, or mortality rates.
PubMed: 36554089
DOI: 10.3390/healthcare10122566 -
World Journal of Cardiology Nov 2022Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral...
BACKGROUND
Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs.
AIM
To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department.
METHODS
A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once.
RESULTS
From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 61.18% in 2019-2021, +25.55%, < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 34.18% in 2019-2021, -15.00%, < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 1.97% in 2021, < 0.0001).
CONCLUSION
Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.
PubMed: 36483763
DOI: 10.4330/wjc.v14.i11.576 -
Journal of Multidisciplinary Healthcare 2022During the last few years, a progressive higher proportion of patients have had upper gastrointestinal bleeding (UGIB) related to antithrombotic therapy. The...
INTRODUCTION
During the last few years, a progressive higher proportion of patients have had upper gastrointestinal bleeding (UGIB) related to antithrombotic therapy. The introduction of direct oral anticoagulant (DOAC) and COVID-19 pandemic may change the incidence, mortality, and follow-up, especially in patients at high risk of bleeding.
PATIENTS AND METHODS
We studied the use of anti-thrombotic therapy (AT) in patients with upper gastrointestinal bleeding for 5 years (January 2017-December 2021) including Covid-19 pandemic period (March 2020-December 2021). We analyzed mortality rate, rebleeding rate and need for transfusion in patients with AT therapy compared with those without AT therapy and risk factors for mortality, and also the incidence of gastrointestinal bleeding in patients admitted for COVID-19 infection.
RESULTS
A total of 824 patients were admitted during Covid-19 pandemic period and 1631 before pandemic period; a total of 426 cases of bleeding were recorded in patients taking antithrombotic therapy and the frequency of antithrombotic therapy in patients with UGIB was higher in pandemic period (24.39% versus 13.8%). Unadjusted mortality was 12.21%, similar with patients with no antithrombotic treatment but age-adjusted mortality was 9.62% (28% lower). The rate of endoscopy was similar but fewer therapeutic procedures were required. Mean Hb level was 10% lower, and more than 60% of patients required blood transfusion.
CONCLUSION
Mortality was similar compared with patients with no antithrombotic therapy, fewer therapeutic endoscopies were performed and similar rebleeding rate and emergency surgery were noted. Hb level was 10% lower and a higher proportion of patients required blood transfusions. Mortality was higher in DOAC treatment group compared with VKA patients but with no statistical significance. The rate of upper gastrointestinal bleeding in Covid-19 positive hospitalized cases was 0.58%. The mortality risk in multivariate analysis was associated with GB score, with no endoscopy performed, with obscure and variceal bleeding and with LMWH versus VKA therapy.
PubMed: 36425876
DOI: 10.2147/JMDH.S380500 -
Medicina (Kaunas, Lithuania) Aug 2022Background and Objectives: Immediate postoperative anticoagulation regimens in patients with mechanical prosthetic valves undergoing non-cardiac surgery are clear only...
Background and Objectives: Immediate postoperative anticoagulation regimens in patients with mechanical prosthetic valves undergoing non-cardiac surgery are clear only for unfractionated heparin (UH), whereas the few low-molecular-weight heparin (LMWH) trials available to date concern the use of Enoxaparin in general/orthopedic surgery. We performed a single-center real-world data study comparing the efficacy and safety of LMWH—Enoxaparin (E)— and UH during the perioperative period in non-cardiac surgical procedures in patients with mechanical prosthetic valve replacement in the mitral, aortic, or tricuspid positions. Materials and Methods: We enrolled 380 patients, who received E or UH together with oral anticoagulation with antivitamin K (acenocoumarol) until they achieved an optimal International Normalized Ratio (INR). Objective assessment of E efficacy included the following: normal value for all the parameters of ultrasound prosthetic functioning, no early thrombosis of the prosthesis, and rapid achievement of target INR with a decreased period of subcutaneous anticoagulation. Subjective assessment included the following: clinical improvement with decreased immobilization and in-hospital stay, fewer gluteal ulcerations, and fewer postoperative depression and anxiety episodes. Results: Comparing with UH, anticoagulation with E was more effective (p < 0.0001 and p = 0.02). The probability of death was smaller in the E group compared with the UH group. No major hemorrhagic event was reported. Mild bleeding episodes and thrombocytopenia were more common in the UH group. Patient’s compliance and quality of life were better with E due to shortened hospitalization, decreased need for testing of coagulation (every 6 h for UH), better dosing (SC every 12 h for E versus continuous infusion for UH), shortened immobilization during the immediate postoperative period with subsequent improvement in the psychological status, as well as due to lack of significant side effects. Conclusions: Taking into consideration the improved efficiency and safety, as well as all the supplementary advantages, such as no need for anticoagulation monitoring, the ease of administration, and reduced duration of hospitalization, E should be seen as an attractive alternative for anticoagulation which deserves further investigation.
Topics: Anticoagulants; Enoxaparin; Heart Valves; Heparin; Heparin, Low-Molecular-Weight; Humans; Quality of Life
PubMed: 36013586
DOI: 10.3390/medicina58081119 -
Patient Preference and Adherence 2022Cardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and...
Effectiveness of a Nursing Intervention Module on Adherence, Knowledge, Quality of Life, and Complications Among Patients Receiving Anticoagulation therapy-a Randomized Controlled Trial Protocol.
BACKGROUND
Cardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and acenocoumarol are the commonly used oral anticoagulants to treat and prevent thromboembolic disorders in patients with cardiovascular diseases. In India, approximately 2-2.5 million patients with rheumatic heart disease are receiving oral anticoagulation therapy. Additionally, this therapy is provided for stroke prevention in the case of atrial fibrillation and the treatment of valvular heart disease, stroke, and deep vein thrombosis. As the therapeutic range of these drugs is narrow and is affected by many factors, their use is challenging. This study aims to evaluate the effectiveness of a nursing intervention module in terms of adherence to therapy, knowledge, quality of life, and complications among patients receiving oral anticoagulation therapy. Furthermore, this study will address factors that affect adherence and the risk for bleeding by using a randomized controlled trial design.
METHODS
This single-blind, single-center, randomized controlled trial will focus on adherence to oral anticoagulation therapy. A total of 320 patients who are on oral anticoagulation therapy will be randomized into blocks and allocated to either the intervention or standard care group. The intervention will comprise the use of a nursing intervention module that includes a booklet, log sheet, and decision aid on oral anticoagulation therapy adherence. Outcome measures, that is, knowledge regarding oral anticoagulation therapy, adherence, complications, and quality of life, will be assessed at the baseline and during follow-ups.
DISCUSSION
Patient safety can be best achieved through patients' adherence to medication dose and monitoring of blood test values. Thromboembolic and bleeding complications are likely to occur when either the patient does not adhere to the treatment or the therapeutic range of the international normalized ratio is not maintained. This study will assess the nonadherence behavior and the effectiveness of a nursing intervention module toward adherence behavior.
TRIAL REGISTRATION
This research project is registered under the Clinical Trial Registry of India (CTRI/2019/06/019610).
PubMed: 35903081
DOI: 10.2147/PPA.S365585 -
Prilozi (Makedonska Akademija Na... Jul 2022Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous...
Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for () in the first patient, his brother (the second case) was compound heterozygote for PTB and for , and his sister (third case) was heterozygous only for the mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for ) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.
Topics: Acenocoumarol; Anticoagulants; Female; Heparin; Humans; Male; Rivaroxaban; Thrombophilia; Thrombosis; Venous Thromboembolism; Venous Thrombosis
PubMed: 35843922
DOI: 10.2478/prilozi-2022-0016 -
The Journal of International Medical... Jun 2022Effective prevention of thromboembolism is essential for patients with mechanical prosthetic heart valves. For this group of patients, vitamin K antagonists (VKAs)...
Effective prevention of thromboembolism is essential for patients with mechanical prosthetic heart valves. For this group of patients, vitamin K antagonists (VKAs) remain the drug group of choice despite the widespread use of new anticoagulants in other diseases. As a consequence, warfarin resistance remains a serious challenge for physicians. The current report describes a 65-year-old male patient that had a mechanical prosthetic aortic valve implanted due to severe aortic insufficiency after infective endocarditis. Despite consistent increases in his warfarin dose, the level of international normalized ratio (INR) remained very low. The patient was considered to have warfarin resistance. Warfarin was successfully replaced by another VKA, acenocoumarol, which resulted in a stable INR observed over 1 year of follow-up. Achieving the target INR in patients with mechanical prosthetic heart valves using VKAs is the main goal of thromboprophylaxis. Although the genetic changes that cause warfarin resistance are understood, the options to overcome these pharmacogenetic issues remain limited. Based on the success with this current patient, physicians with similar patients with warfarin resistance might wish to consider replacing warfarin with acenocoumarol.
Topics: Acenocoumarol; Aged; Anticoagulants; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Metabolism, Inborn Errors; Venous Thromboembolism; Warfarin
PubMed: 35748017
DOI: 10.1177/03000605221103959